Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Thursday, May 31, 2012

I was shocked when Dr. Oz recommended a snack made with agave syrup. I had seen a previous program by America's representative of the medical industry in which he revealed the hazards of agave syrup as a new source of fructose. Now he just skipped over the use of this fructose syrup as a "natural" sweetener, even though it is even less healthy than high fructose corn syrup, HFCS. There seems to be a lot of deliberate confusion about sweeteners and since I am trained as a carbohydrate chemist, I will try to tell it as I see it.

General Information

Carbohydrates are not needed in your diet, since your liver can make all the blood sugar that you need from protein. Most diabetics can benefit from a low carbohydrate diet.

Fructose in any form (HFCS, sucrose, agave syrup) contributes to liver damage. Fructose is the most chemically reactive sugar.

Artificial sweeteners, especially in soft drinks, do not contribute dietary calories, but they apparently increase insulin production and contribute to hunger, eating and obesity.

Insulin production removes glucose from the blood, i.e. lowers blood sugar, by increasing glucose transport into fat cells. If glucose is in your blood, but insulin is not present, e.g. type I diabetes, then you get thin. If glucose is in your blood and insulin is present, then you get fat. If you are fat and glucose is still high in the blood and insulin is present, then the fat cells will die unless they shut off the insulin response, i.e. insulin resistance.
Lowering the amount of carbohydrates, sweeteners/starch, in your diet makes it easier to control blood sugar levels and avoid hunger.

Decreasing dietary carbohydrates means that calories have to be present in some other form and the answer is saturated fat. Most polyunsaturated fats, e.g. vegetable oils, except olive oil, are not healthy. The fats in meat, butter, eggs and coconut oil are the healthy choices supported by the biomedical literature, and along with vegetables, form the foundation of a healthy, anti-inflammatory diet.

Central Metabolism Started with Fructose not Glucose
All organisms convert sugars through a common series of enzymatic steps, called central metabolism, to a simple, three-carbon compound called pyruvate. Pyruvate can be used as a source of energy in mitochondria in the presence of oxygen or converted into alcohol or acids in various forms of fermentation. No matter what sugars are used, e.g. glucose, galactose, mannose, they are all converted in cells into derivatives of fructose. Thus, fructose is common to all organisms and can be considered to be the most primitive. So why is glucose usually considered to be the the start of central metabolism and why is dietary fructose dangerous?

Fructose is too Reactive to Transport
The first cells used fructose as the starting material to make the building block molecules of cells, e.g. carbs, proteins, fats, nucleic acids, and energy in the form of ATP. Multicellular organisms, such as animals and plants had to move sugars from cell to cell. It would be obvious to transport fructose, since all other molecules could be converted into fructose, but the problem is that fructose is too chemically reactive, i.e. it reacts with proteins to form AGE. It is for that reason that fructose is converted by cells into glucose, which is less than one tenth as chemically reactive. In plants, the reactive groups of glucose and fructose are bonded together to produce sucrose, table sugar, which is much less reactive and can be transported in plant vessels at very high concentrations.

High Blood Sugar is Bad, High Fructose is Worse (AGE-ing)
High levels of blood sugar, glucose, react with proteins to produce advanced glycation end products, AGE. Fructose in the blood produces these inflammatory compounds more than ten times faster. That is why fructose is a bad sweetener for diabetics. Eating fructose, e.g. agave syrup or sucrose, doesn't directly raise blood sugar/glucose levels, since it raises blood fructose levels, which is worse.

Fructose Fattens Livers
Fructose is rapidly absorbed in the intestines and transported to the liver. The blood vessels of the liver remove fructose from the blood and it is rapidly converted into fat. Fructose in sweeteners has now surpassed alcohol as the major source of liver disease.

Sweeteners
Fructose is ten times sweeter than glucose, and that is why cheap forms of glucose, such as corn syrup, are treated with enzymes to convert some of their glucose into fructose to produce high fructose corn syrup. Corn syrup is not as sweet as pure glucose, because the syrup contains a mixture of short chains of glucose of different lengths, and the chains decrease in sweetness with length. By changing some of the glucose into fructose, the HFCS can be made as sweet as table sugar, sucrose. Corn subsidies keep corn syrup cheap and make HFCS very profitable. Unfortunately, the HFCS contains fructose and therefore it has the liver toxicity and AGE-forming inflammation of fructose. Agave syrup is like HFCS on steroids.

Agave Syrup is Fructose
Agave syrup contains fructose produced by industrial processing of the fructose polysaccharides, inulin, in agave extracts. I cannot understand why anyone would use this commercially processed fructose as a sweetener. It doesn't raise blood sugar as much as sucrose, because there is much more fructose than sugar (like very high fructose corn syrup) it raises blood fructose levels instead, which is much, much worse.

Sugar Makes You Hungry
The human body can only use simple sugars, e.g. glucose, fructose, sucrose, or starch. Body enzymes convert sucrose into fructose + glucose, and starch into glucose. Other carbs, such as soluble fiber, are only digested by gut bacteria in the colon. The conversion of starches to glucose begins with enzymes in saliva in the mouth and is completed in the upper part of the digestive tract. Starch should be considered as a simple sugar, because it causes a rapid rise in blood sugar, just like glucose. It may actually be faster than table sugar. The rapid rise of blood sugar causes a rapid increase in blood insulin, which in turn rapidly removes sugar into fat cells. The rapid rise and fall of blood sugar provides the experience of hunger. That is why cereal, e.g. oat meal, in the morning produces intense hunger just a few hours later. Actually, oat meal is not quite as unhealthy as most cereals, because it also has some soluble fiber to feed gut flora. A protein and fat breakfast, e.g. bacon and eggs, does not produce rapid hunger, because it does not produce a large insulin rise and glucose fall.

Insulin Resistance is Better than Death by Glucose
As fat cells accumulate glucose as a result of blood sugar transported into the cells in response to insulin, more and more of the glucose is converted into fructose and on to pyruvate. The pyruvate accumulates in mitochondria and ATP production is saturated. This is potentially lethal for the cells, because the conversion of pyruvate into ATP is accomplished by removing high energy electrons as the pyruvate is converted to carbon dioxide. The high energy electrons accumulate in the inner membranes of the mitochondria and if they are not systematically converted to low energy electrons and dumped onto oxygen to produce water, reactive oxygen species, ROS are produced and the result is inflammatory oxidative stress. Antioxidants would be needed to protect from major cellular and organ damage. The cells protect themselves by responding to the accumulation of high energy electrons on the mitochondria by shutting down the response to insulin and blocking further intracellular glucose accumulation. This is insulin resistance.

Carbs: Never too Low
Dietary carbs, such as sugars and starches are not needed, because the liver can convert protein into glucose. Thus, diabetics, who have a hard time balancing their dietary intake of carbs with the insulin that they inject, can simplify the process by routinely eating less carbs spread through many meals and triggering some glucose production by the liver. Craving for carbohydrates/sweets can be dramatically reduced simply by eating fewer carbs and avoiding insulin production that can lead to more dramatic swings of blood sugars and hunger. Using this strategy, I am hungry less than once a week.

Healthfulness of Sweeteners
--from Most Healthy....

Stevia - is a diterpene glycoside (I previously made the silly error of listing it as a protein) (erythritol, another simple sugar alcohol is added to make the stevia granular) that is sweet, doesn't raise blood sugar, no insulin spike and no AGE

Glucose - raises blood sugar, spikes insulin and produces AGE

Xylitol - is a sugar alcohol that inhibits dental bacteria, doesn't raise blood sugar, no insulin spike or AGE

Thursday, May 10, 2012

Milk is a very special food for mammalian babies. It provides essential nutrients; stimulates development of the gut; promotes the growth of the unique neonate gut flora; and kills everything else. Milk is anti-bacterial, anti-fungal and anti-viral. It is used in fruit orchards as a pruning tool dip to prevent the spread of disease between trees, and it is used as a foot dip after ceremonial walking on hot coals. But is cow's milk healthy for adult humans and is milk compromised by pasteurization and homogenization?

Mother's Milk is Fierce
Milk as it is transferred from breast to baby is loaded with molecular weapons for the protection of the baby's respiratory and digestive systems. Cells from the mother are transferred along with the milk and quickly spread out on the surface of the mouth and digestive system to patrol for pathogens. The mother's immune system detects potential risks as the baby's mouth contacts the mother's lymphatic system at the breast, and the antibodies that are subsequently produced are transferred into the milk. Enzymes in the milk digest bacterial cell walls and other milk proteins are converted into anti-bacterial peptides in the baby's stomach before ultimately being digested into amino acid nutrients. Many of the fat/lipid nutrients in milk are also anti-bacterial or anti-viral. Most of the carbohydrate in milk is the simple disaccharide lactose that most bacteria can't use for food. The remaining 10% of the carbohydrates are extensions of the lactose to make galacto-oligosaccharides (GOS, a.k.a. bifidus factor) that are toxic to all but the few bacterial species that make up the highly specialized microbial community of the human baby gut flora. (Cow's milk has an entirely different composition, e.g. lacks bifidus factor, and supports a different gut flora.)

Milk is Liquid Fat
It is hard to transport fat in water, because it isn't soluble. That is true for blood or milk. We have all heard about good and bad cholesterol, LDL and HDL, and the problems of transporting blood lipids from gut to liver to tissues. Specialized carrier proteins are needed for lipid transport in blood and the same is true for milk. Caseins are the milk proteins that coat droplets of fats that make milk white and then form digestible curds in response to the baby's stomach acid and digestive enzymes. We exploit the natural curd forming response of milk proteins and lipid droplets to form yogurts and cheeses.

Pasteurization and Homogenization Put Milk in the Dairy Case
Milk behaves optimally when immediately transferred from the mother's mammary tissue to the baby's digestive tract. Bacteria that contaminate breast milk are quickly killed by cellular and molecular defenses of the milk itself. Thus, breast milk has a long storage life at room temperature, chilled or frozen. The natural defenses of milk also permit regional milk banks, where donated milk is minimally processed and screened, for subsequent use by hospitals to avoid problems, such as necrotizing colitis, associated with the use of artificial feeding substitutes. Commercial preservation of cow's milk in stores has resulted in attempts to extend the shelf-life by heat treatment (pasteurization) to provide additional protection from microbial contamination and homogenization to prevent curd formation.

Milk is for Babies
So why isn't milk the perfect food? Part of the reason may come from the highly specialized and essential role of milk for mammals like people. Millions of years of extreme selection pressure have made sure that every woman produces ample milk for all of her babies. Until very recently, if the baby could not successfully nurse, it would die. That made breast milk the perfect food for babies and milk was integral to the development of the baby gut, baby gut flora and baby immune system. But that didn't mean that cow's milk would be a healthy commercial food for human adults.

Milk Processing May Accentuate Casein Amyloid Fiber Formation
Proteins are made of a long sequence of a thousand amino acids. At each of those thousand positions there is one of twenty different amino acids. Some of the amino acids are hydrophilic and bind to water, whereas other amino acids are hydrophobic and bind only to lipids. Proteins in water fold and unfold in thousands of alternative configurations until the final shape is reached in which there is not enough energy in the molecular vibrations and movements of the water molecules to knock the protein into an alternative shape.

Heating/pasteurization and torturous mixing/homogenization can force milk casein and fats into new configurations that make the proteins stackable into fibers/amyloids. These milk protein fibers may be of interest, because protein fibers are important in many diseases, e.g. type I diabetes, Alzheimer's disease. The problem with amyloids, is that these fibers form a natural repetition of the same amino acid on each of the stacked proteins. This repetitive amino acid, e.g. positively charged lysine or arginine, can provide a binding site for a similarly spaced, oppositely charged molecule, such as heparin, which is involved in dragging molecules from the surface into cells. Beta amyloid fibers with positively charged amino acids in a band along their edges are what kills nerve cells in Alzheimer's disease.

Research has recently demonstrated that milk casein forms amyloid fibers in response to pasteurization and homogenization. It would be interesting to know if these fibers bind to heparin and if these fibers are toxic to intestinal cells.

I have raw cream from grass fed cows in my morning coffee and my three daughters never tasted formula.

Saturday, May 5, 2012

The production of endorphins in tissues in response to nerve stimulation relieves inflammation and pain. Dr. Oz and the medical community seem to forget that hot and cold receptors in the skin can be readily triggered by natural products in foods, to stimulate the release of endorphins and treat inflammation in nearby tissues.

Hot and Cold Don't Easily Penetrate the Skin
Athletic trainers commonly apply hot and cold packs to avoid swelling and inflammation from injuries, and they are always discussing the virtues of various hot/cold regimens. They ignore the extraordinary efficiency of the circulatory system in regulating tissue temperatures and avoiding temperature changes. They also ignore the fact that chemical "hot and cold" salves and ointments are effective without actually changing the temperature of the skin. The essential observation is that triggering hot and cold sensing nerves is more important than changing the temperature of the damaged tissues.

Common Food Molecules Activate Hot/Cold Nerve Receptors
Peppers are hot, because they contain capsaicin that binds to protein receptors on nerves in the skin, which results in the brain sensation of heat. Camphor and castor oil bind to the same receptors. Menthol binds to corresponding cold receptors. Vicks Vaporub has both menthol and camphor, and therefore stimulates both hot and cold sensors. Vicks is also an effective treatment for tissue inflammation.

Vicks and Castor Oil are Effective Treatments for Pain and Inflammation
A bee sting or a burn on a finger will produce reddening, swelling and pain, that can be quickly alleviated by applying Vicks to the wrist. The hot and cold sensors of the wrist would be stimulated and the returning nerve signals would be generally detected in the whole hand and produce endorphins that would calm the inflammation and sooth the injured finger. In a similar way, an inflamed joint can be treated by topical menthol and castor oil, and lower abdominal discomfort can be alleviated by castor oil applied to the belly.

Tendonitis can be Treated with Peppermint Soap
I have treated a persistent tendonitis in my shoulder by applying Dr. Bronner's Peppermint Soap liberally to my shoulder and waiting a few minutes before continuing my shower. This gentle, persistent treatment produced relief within a week. This was a cure for this persistent inflammation and pain. It also works on joints.

What Dr. Oz needs to communicate is that there are simple ways to stimulate hot/cold receptors that have nothing to do with changing the temperature of deeper tissues, but these treatments are very effective in stimulating general endorphin production that reduces troublesome inflammation and pain. As an addendum, vagal stimulation, i.e. through yoga postures such as shavasana or the Valsalva maneuver, can produce a reduction in general inflammation.

Friday, May 4, 2012

I was not expecting my recent reading of an article on femtosecond reaction kinetics to produce another discussion of quorum sensing, biofilms and vitamins. The idea behind the article was to identify new targets for drug design based on the ephemeral transition states that occur as enzymes bind substrates, stabilize transition states and yield product molecules. Drugs that mimic the transition states make good enzyme inhibitors. One of the target enzymes for the control of disease is an enzyme, MTAN, involved in the synthesis of quorum sensing molecules that orchestrate the construction of common biofilms. The idea is to inhibit MTAN and also avoid selection for antibiotic resistance. Unfortunately, targeting quorum sensing molecules also may produce vitamin deficiencies, since many of these molecules, in this case vitamin K, are also quorum sensing molecules.

Drugs have too many Side Effects
Specificity in the binding of molecules to the thousands of proteins that are coded by the ca. 20,000 human genes depends on a very tight fit between the molecular "key" and the binding site "lock" of the protein. Just as in physical world, a small key/drug molecule with limited surface detail is not as safe/specific as a larger key with many surface features, and a larger lock/enzyme active site that is harder to pick/has fewer interactions with random enzymes. Unfortunately, most drugs are small molecules with limited surface features that make them like molecular skeleton keys that produce many side effects by interacting with unintended proteins/enzymes.

Transition States are more Specific
A recent focus on drug research is to exploit molecular computation and modeling to design molecules that will bind to the part of an enzyme that actually participates in binding substrates and catalyzing chemical reactions. These designed molecules can interact with an expanded region of the enzyme and bind more strongly than the normal substrate. The designed molecules can be very effective inhibitors that will not react as nonspecifically as inhibitors identified by trial an error, e.g. statins.

Biofilm Inhibitors are Targets for Antibiotic Development
The enzymes involved in the synthetic pathways of biofilm quorum sensing signals have been identified and powerful inhibitors of some of these enzymes have now been designed and synthesized. These inhibitors are very effective in inhibiting biofilm formation by some common bacterial pathogens (and essential gut flora.)

Biofilm Inhibitors will also Block Vitamin Production in Gut Biofilms
The new biofilm inhibitor antibiotics may have enhanced specificity, but they target enzymes that also provide essential functions in biofilms that are needed for healthy gut and immune system function. Many of the vitamins that are produced by gut flora are also quorum sensing signal molecules in healthy gut biofilms. Thus, blocking MTAN to block biofilm formation of a pathogen, will also block gut synthesis of vitamin K, which is made in gut bacteria using the MTAN pathway. These inhibitors would be expected to be particularly damaging to the specialized gut flora of breastfed babies, since these gut bacteria are known producers of vitamin K.

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.